Blocking Signalopathic Events to Treat Cerebral Cavernous Malformations.

Trends in Molecular Medicine
Salim Abdelilah-SeyfriedW Brent Derry

Abstract

Cerebral cavernous malformations (CCMs) are pathologies of the brain vasculature characterized by capillary-venous angiomas that result in recurrent cerebral hemorrhages. Familial forms are caused by a clonal loss of any of three CCM genes in endothelial cells, which causes the activation of a novel pathophysiological pathway involving mitogen-activated protein kinase and Krüppel-like transcription factor KLF2/4 signaling. Recent work has shown that cavernomas can undergo strong growth when CCM-deficient endothelial cells recruit wild-type neighbors through the secretion of cytokines. This suggests a treatment strategy based on targeting signalopathic events between CCM-deficient endothelial cells and their environment. Such approaches will have to consider recent evidence implicating 'third hits' from hypoxia-induced angiogenesis signaling or the microbiome in modulating the development of cerebral hemorrhages.

Citations

Sep 11, 2020·Journal of Developmental Biology·Matthew BuechnerHikmat Al-Hashimi
Nov 26, 2020·Open Biology·Valerie L Su, David A Calderwood
Mar 15, 2021·Current Opinion in Hematology·Claudia Jasmin Rödel, Salim Abdelilah-Seyfried

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cavernous Hemangioma

Cavernous hemangioma is a blood vessel defect or benign tumor that leads to leakage of blood to the surrounding tissues. This can occur in several organs including the brain, which can lead to seizures. Discover the latest research on cavernous hemangiomas here.

Related Papers

The New England Journal of Medicine
Ithamar Ganmore, Anat Achiron
The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques
I FleetwoodM Hudon
The New England Journal of Medicine
Archives of Neurology
K S Lee, R F Spetzler
Stroke; a Journal of Cerebral Circulation
Atif ZafarL A Morrison
© 2021 Meta ULC. All rights reserved